The object of the proposed study is to determine the biological attributes and function of gut associated lymphoid tissues. Through the proposed study, information will be gained toward the understanding of immunity of enteric disease and the means of enhancing it. Also the development of allergies associated with the alimentary tract, and the possibly mandatory presence of the autochthonous flora for expanding lymphoid cell populations will be elucidated. These questions will be approached firstly through a systematic study of the biology of the thymus-dependent (T cell) lymphoid tissue of the intestinal tract. Secondly, the stimulatory and modulatory effects of the intestinal flora on this tissue will be investigated. The homing or migratory pathways of Peyer's patch T cells will be initially studied using immunological and radioactive labels. Then the immunologic function of Peyer's patch T cell will be investigated by assessing the ability of Peyer's patch cells to reconstitute T cell deficient mice as determined by the ability of the reconstituted mice to demonstrate evidence of cell-mediated immunity in a number of test systems. In addition to the Peyer's patches, a large population of T lymphocytes reside in the small intestinal mucosa between mucosal epithelial cells. These intra-epithelial lymphocytes will be characterized using specific antisera developed against T cells as well as by determining their turnover time and migratory characteristics. The effects which the intestinal flora has on the gut lymphoid tissues will be elucidated by studying T cell dependent responses, such as delayed hypersensitivity and cell-mediated immune responses, in gnotobiotic mice, rats, and guinea pigs. It is anticipated that such studies will have bearing on human intestinal disorders suspected of being immune response disorders, such as Crohn's disease and ulcerative colitis.